DESCRIPTION: (provided by the applicant) The K-25 funding mechanism is designed to foster the career of quantitative scientists who wish to focus their research endeavors on behavioral or biomedical research. Toward this objective I propose to utilize my biomedical engineering background while acquiring the knowledge and skills necessary to become a competitive independent investigator in the area of functional magnetic resonance imaging (fMRI) with a particular focus on problems related to imaging of children. The potential of fMRI, a non-invasive technique for evaluating brain functioning, as a powerful tool in studying brain development is consensually recognized. This tool will also prove to be invaluable when applied toward elucidating the predisposing factors and consequent effects of drug abuse. Significant obstacles, however, mitigate the application of fMRI techniques in very young children and in children with high behavioral activity levels, as is often the case in children at high risk for substance use disorders (SUDs). The field currently needs interdisciplinary scientists with quantitative backgrounds to address these methodological obstacles of fMRI and thereby make fMRI studies of these children feasible . In order to establish a research career dedicated to this task, I will obtain additional training in 1) fMRI methodologies with a focus on overcoming limitations of carrying out this technique in children, 2) developmental neuroscience and neuroanatomy, and 3) neuroscience pertaining to central nervous system (CNS) mechanisms underlying the vulnerability to drug abuse. By focusing on these areas I will become a skilled and independent interdisciplinary scientist bridging quantitative fMRI methodological problems and developmental neuroscience research with a particular focus on CNS vulnerability to SUD. I will also initiate a series of fMRI studies to address some of the main methodological problems of imaging in children exhibiting behavioral dysregulations, a key factor in SUD. Children at high risk for SUD will be studied using the methodological advances developed in this project. The proposed research offers the prospect for increasing the reliability of fMRI data in studying both normal and pathological development. Methodological improvements in fMRI will be of use to other types of clinical populations besides youth at risk for SUD, thereby making this technique more generalizable for developmental neuroscience investigations.